Research Update:Angelica dahurica.

  seminal trace...Angelica dahurica root Extract.10:1.Radix Angelicae Dahuricae.Baizhi,Hang Bai Zhi,Radix Angelicae Dahuricae,Dahuricae Angelica Root,Root of Dahuricae Angelica,Root of Scabrous Cowparsnip...

 


   Phytochemical info of Rhizoma Polygonati or Angelica dahurica.

 Product Name:
 Synonym:
 Definition:Angelica dahurica are majorly composed of
 Chemical information disclosed as following table:


   Research Update:Angelica dahurica.

  High-performance liquid chromatographic method for the determination and pharmacokinetic study of oxypeucedanin hydrate and byak-angelicin after oral administration of Angelica dahurica extracts in mongrel dog plasma.:J Pharm Biomed Anal. 2007 May 9;44(1):166-72. Epub 2007 Feb 8.Xie Y, Chen Y, Lin M, Wen J, Fan G, Wu Y.Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai 200433, PR China.

 A high-performance liquid chromatographic method was developed and validated for the determination and pharmacokinetic study of oxypeucedanin hydrate and byak-angelicin after oral administration of Angelica dahurica extracts in mongrel dog plasma. The coumarin components and the internal standard isopsoralen were extracted from plasma samples with the mixture of tert-butyl methyl ether and n-hexane (4:1, v/v). Chromatographic separation was performed on a C(18) column (200 mm x 4.6mm, 5 microm) with the mobile phase acetonitrile-methanol-water-acetic acid (20:15:65:2, v/v/v/v) at a flow-rate of 1.0 ml/min. Only the peak of oxypeucedanin hydrate and byak-angelicin could be detected in dog plasma after oral administration of ethanol extracts of A. dahurica mainly containing xanthotoxol, osthenol, imperatorin, oxypeucedanin hydrate and byak-angelicin. The calibration curves of oxypeucedanin hydrate and byak-angelicin were linear over a range of 22.08-8830.00 and 6.08-2430.00 ng/ml in dog plasma, respectively. The quantification limit of oxypeucedanin hydrate and byak-angelicin in dog plasma was 22.08 and 6.08 ng/ml, respectively. The intra- and inter-day precision was less than 7.6% and 8.5% and the accuracy was from 91.9% to 106.1%. The lowest absolute recoveries of oxypeucedanin hydrate and byak-angelicin were 85.7% and 87.0%, respectively. The method was successfully applied to the pharmacokinetic studies of oxypeucedanin hydrate and byak-angelicin in dog plasma after oral administration of ethanol extracts from A. dahurica.

  Ethyl acetate extract from Angelica Dahuricae Radix inhibits lipopolysaccharide-induced production of nitric oxide, prostaglandin E2 and tumor necrosis factor-alphavia mitogen-activated protein kinases and nuclear factor-kappaB in macrophages.:Pharmacol Res. 2007 Apr;55(4):263-70. Epub 2006 Dec 19.

 Angelica dahurica (Umbelliferae) has been used to treat headache of common cold, supraorbital neuralgia, painful swelling on the body, nasal stuffiness, leukorrhea and arthralgia due to wind-dampness in Korean traditional medicine. It is also claimed to be effective in the treatment of acne, erythema, headache, toothache, sinusitis, colds and flu. The present study focused whether the ethyl acetate extract from Angelica Dahuricae Radix (EAAD) inhibits production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor (TNF)-alpha, as well as expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated macrophages. EAAD inhibited LPS-induced NO, PGE(2) and TNF-alpha production as well as expression of iNOS and COX-2 in RAW 264.7 cells. EAAD inhibited LPS-induced TNF-alpha production in THP-1 cells. Furthermore, EAAD suppressed LPS-induced phosphorylation of p38 MAPK and extracellular-signal regulated kinases 1/2 (ERK1/2), I-kappaBalpha degradation, and NF-kappaB activation in RAW 264.7 cells. These results suggest that EAAD has the inhibitory effects on LPS-induced TNF-alpha, NO and PGE(2) production, and expression of iNOS and COX-2 in macrophage through blockade in the phosphorylation of MAPKs, following I-kappaBalpha degradation and NF-kappaB activation.

  Studies on cultivation measures of Angelica dahurica.:Zhong Yao Cai. 2006 Nov;29(11):1127-8. Chinese.Zhang ZM, Guo YH, Zhai ZX, Deng SJ, Zhao ZM, Fu XM, Bu YY, Zhao YH, Yang CQ.Chinese Medicinal Herbs Research Center, China Agricultural University, Beijing 100094, China.

 OBJECTIVE: To evaluate the effect of seedingtime, density of crop and fertilization on the yield of Angelica dahurica. METHOD: Use weighing method to measure the output of A. dahurica. RESULT: The highest yield of seeding-time is 8373 kg/hm' on April 20, which is considerably different compared with April 5 and May 5; the highest yield of the density is 9300 kg/hm2 on 330,000 plants/hm2; the yield of fertilization tests all are considerable higher than that of the contrast. CONCLUSION: The appropriate seeingtime of A. dahurica is the first or second ten days of April, the appropriate density is 330,000 plants/hm2, and the appropriate amount of fertilization is N24P20, i.e pure N 360 kg and P20, 300 kg per hectare.

  Antiproliferative effect of furanocoumarins from the root of Angelica dahurica on cultured human tumor cell lines.:Phytother Res. 2007 Mar;21(3):288-90.

 A bioassay-guided fractionation of the root extract of Angelica dahurica (Umbelliferae) led to the isolation of six furanocoumarins as active ingredients responsible for the antitumoral property. The hexane soluble part of the extract demonstrated a significant inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nervous system) and HCT-15 (colon) in vitro, whereas the remaining water soluble part exhibited poor inhibition. Intensive investigation of the hexane soluble part of the extract yielded six furanocoumarins, i.e. isoimperatorin, cnidicin, imperatorin, oxypeucedanin, byakangelicol, oxypeucedanin hydrate, all of which exhibited a significant inhibition on cell proliferation in a dose-dependent manner.

  Estrogenic activity of furanocoumarins isolated from Angelica dahurica.:Arch Pharm Res. 2006 Sep;29(9):741-5.Piao XL, Yoo HH, Kim HY, Kang TL, Hwang GS, Park JH.School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.

 In our efforts to discover novel phytoestrogens to treat menopausal symptoms, eleven furanocoumarins were isolated from Angelica dahurica and tested for their estrogenic activity on the Ishikawa cell line. Among the compounds tested, 9-hydroxy-4-methoxypsoralen and alloisoimperatorin showed strong abilities to induce alkaline phosphatase (AP) with EC50 values of 1.1 and 0.8 microg/mL, respectively, whereas the other nine furanocoumarins were weakly or only slightly active.


  The prescriptions frequencies and patterns of Chinese herbal medicine for allergic rhinitis in Taiwan.:Allergy. 2006 Nov;61(11):1316-8.Kung YY, Chen YC, Hwang SJ, Chen TJ, Chen FP.Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

 BACKGROUND: The evaluation of Chinese herbal medicines (CHM) to allergic rhinitis (AR) by large-scale pharmaco-epidemiological study is not ease found, although CHM had been reported to have potential effect for AR in some clinical trials. AIMS OF THE STUDY: To explore the frequency and pattern of CHM prescriptions on AR, we have the study by analysing the population-based CHM database in Taiwan. METHODS: The way for this study was linked and processed the complete traditional Chinese medicine database for Taiwanese recorded in the year 2002. The diagnosis of AR was extracted with the only single ICD-9 Code of 477 to calculate the frequency and pattern of prescriptions. Association rule was applied to analyse co-prescription of CHM for patients with AR. RESULTS: In the year 2002, among the 22 520 776 valid beneficiaries of the National Health Insurance, Taiwan, 914 612 subjects (3.8% of the total valid beneficiaries) have diagnosed AR. There were 35.6% of AR patients been treated by CHM. The peak age of AR patients treated by CHM was at the first decade (0-10). For the AR patients, the most common Chinese herbal formula prescription was Shin-yi-qing-fei-tang, or Angelica dahurica (Bai-zhi) for the single Chinese herb. While for the combination treatments the most common prescription was the two formulae, Xiao-qing-long-tang and Shin-yi-san. CONCLUSIONS: Because of the high utilization rate of the CHM treatment for AR, a large-scale randomized trial warrants further research for its efficacy and safety.

  New cosmetic agents for skin whitening from Angelica dahurica.:J Cosmet Sci. 2006 Jan-Feb;57(1):11-21.

 To develop a new whitening agent for cosmetics from natural products, Angelica dahurica was selected for its inhibitory effect on melanogenesis in B16 melanoma cells. From the mechanism study, it was clarified that the ethanolic extracts of this plant showed the suppression of tyrosinase synthesis but no inhibition of tyrosinase activity. In order to find the active constituents from this plant, the ethanol extracts were chromatographed repeatedly with silica gel. Two coumarin compounds were isolated from A. dahurica. Their structures were identified by physicochemical and spectral data such as UV, IR, NMR, and MS. It was shown that the active substance was isoimperatorin (10-[(3-methyl-2-butenyl)oxy]-7H-furo[3,2-g][1] benzopyran-7-one) and imperatorin (9-[(3-methyl-2-butenyl)oxy]-7H-furo[3,2-g][1] benzopyran-7-one). They significantly inhibited tyrosinase synthesis in B16 melanoma cells. To elucidate the action mechanism of the active compounds of A. dahurica, we investigated the changes in the mRNA level of tyrosinase using the RT-PCR technique. As a result, the mRNA level of tyrosinase was markedly reduced by active compounds of A. dahurica. From these results, we suggest that these extracts might be useful as a new whitening agent in cosmetics, but the in vitro findings must be verified in in vivo skin-lightening studies.

  Preparative isolation of imperatorin, oxypeucedanin and isoimperatorin from traditional Chinese herb "bai zhi"Angelica dahurica (Fisch. ex Hoffm) Benth. et Hook using multidimensional high-speed counter-current chromatography.:J Chromatogr A. 2006 May 19;1115(1-2):112-7. Epub 2006 Mar 20.Wei Y, Ito Y.Applied Chemistry Department, Faculty of Sciences, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Chaoyang District, Beijing 100029, China.

 Preparative high-speed counter-current chromatography (CCC) was successfully used for isolation and purification of imperatorin, oxypeucedanin and isoimperatorin from traditional Chinese herb "bai zhi"Angelica dahurica (Fisch. ex Hoffm) Benth. et Hook using multidimensional counter-current chromatography with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at volume ratios of 1:1:1:1 (v/v) and 5:5:4.5:5.5 (v/v), which had been selected by analytical high-speed counter-current chromatography (HSCCC). Using two preparative units of the CCC centrifuge, which are connected by a column switching valve, about a 300 mg amount of the crude extract was separated, yielding 19.9 mg of imperatorin, 8.6 mg of oxypeucedanin and 10.4 mg of isoimperatorin all at a high purity of over 98%.

  Separation and quantitative analysis of coumarin compounds from Angelica dahurica (Fisch. ex Hoffm) Benth. et Hook. f by pressurized capillary electrochromatography.:J Pharm Biomed Anal. 2006 Apr 11;41(1):105-16. Epub 2005 Nov 28.Chen Y, Fan G, Chen B, Xie Y, Wu H, Wu Y, Yan C, Wang J.Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai, PR China.

 A pressurized capillary electrochromatography (pCEC) method with post-column detection cell has been developed for the therapeutically important coumarins from Angelica dahurica extract. The separation of five major coumarins (xanthotoxol, osthenol, imperatorin, oxypeucedanin hydrate, byakangelicin) was optimized with respect to composition of the mobile phase, ionic strength of buffers, pH, and applied voltage. Baseline separation was achieved for the five coumarins in less than 25 min using a mobile phase of methanol-acetonitrile-phosphate buffer (pH 4.8; 15 mM) (22.5:15:62.5, v/v/v). The method showed satisfactory retention time and peak area repeatability with the first use of post-column detection cell in the pCEC instrument. Comparing to capillary high performance liquid chromatography (capillary HPLC) and conventional high performance liquid chromatography (HPLC), higher column efficiency, and shorter analysis time were achieved in pCEC. The five coumarins in the extract samples representing different stages of traditional extraction of A. dahurica were also quantitatively analyzed by pCEC. The calibration curves were linear in the range 37-129, 36-126, 12-41, 88-306, 20-69 microg/ml of the standard solutions containing the five coumarins with correlation coefficients between 0.9976 and 0.9994.

  In vitro GABA-transaminase inhibitory compounds from the root of Angelica dahurica.:Phytother Res. 2005 Oct;19(10):839-45.

 The 80% aqueous MeOH extracts from the root of Angelica dahurica, found to inhibit the activities of GABA degradative enzymes GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH), were fractionated using EtOAc, n-BuOH and H2O. Repeated column chromatography for the EtOAc and n-BuOH fractions led to the isolation of two new coumarins, oxypeucedanin hydrate-3''-butyl ether and isopraeroside IV along with six known coumarins, isoimperatorin, imperatorin, phellopterin, oxypeucedanin hydrate, nodakenin and 3'-hydroxymarmesinin, and two polyacetylenes, falcarindiol and octadeca-1,9-dien-4,6-diyn-3,8,18-triol. Of the isolated pure compounds, imperatorin and falcarindiol inactivated the GABA-T activities in both time- and concentration-dependent manners. The kinetic studies showed that imperatorin and falcarindiol reacted with the GABA-T with a second-order rate constant of 2.3 +/- 0.2 mm(-1) min(-1) and 1.5 +/- 0.1 mm(-1) min(-1), respectively. It is postulated that imperatorin and falcarindiol are able to elevate the neurotransmitter GABA levels in the central nervous system by an inhibitory action on the GABA degradative enzyme GABA-T.


  Melanogenesis stimulation in murine b16 melanoma cells by umberiferae plant extracts and their coumarin constituents.:Biol Pharm Bull. 2005 Jul;28(7):1229-33.

 Melanogenesis stimulation activities of seven ethanolic extracts obtained from Umbelliferae plants used as Chinese crude drugs, namely the roots of Angelica dahurica BENTH. et HOOK., A. biserrata SHEN et YUAN, Notopterygium incisum TING, Heracleum lanatum MICHX., and H. candicans WALL., and the fruits of Cinidium monnieri (L.) CUSSON and C. formosanum YABE, were examined by using cultured murine B16 melanoma cells. Among them, the extract (5, 25 microg/ml) of H. lanatum showed a potent stimulatory effect on melanogenesis with significant enhancement of cell proliferation in a dose-dependent manner. The melanogenesis stimulatory effects of sixteen coumarins (1-16) isolated from the seven Umbelliferae crude drugs were also examined. Among them, linear-furocoumarins [psoralen (1), xanthotoxin (2), bergapten (3), and isopimpinellin (4)] and angular-furocoumarin [sphondin (13)] exhibited potent melanogenesis stimulation activity. From the view point of structure-activity relationships, it may be assumed that a linear-furocoumarin ring having a hydrogen and/or methoxyl group at 5 and 8 positions such as 1, 2, 3 and 4 was preferable for the melanogenesis stimulation activity. The introduction of a prenyl group into the furocoumarin ring was disadvantageous. Coumarin derivatives having a simple coumarin ring were inactive.

  Characterization of a cDNA coding for an extracellular calmodulin-binding protein from suspension-cultured cells of Angelica dahurica.:Planta. 2005 Oct;222(3):428-37. Epub 2005 May 13. Mao GH, Hou LX, Ding CB, Cui SJ, Sun DY.Institute of Molecular Cell Biology, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei 050016, People's Republic of China.

 In order to characterize a specific extracellular 21-kDa calmodulin-binding protein (named: ECBP21) from Angelica dahurica L. suspension-cultured cells, the cDNA coding for the protein has been cloned. Here, Southern blot analysis shows that there are at least two copies of ECBP21 gene in Angelica genome. Using truncated versions of ECBP21 and synthetic peptide in CaM binding assays, we mapped the calmodulin-binding domain to a 16-amino acid stretch (residues 200-215) at the C-terminal region. The ECBP21 was localized in the cell wall area by the immunogold electron microscopy and by GFP labeling method. These results define ECBP21 as a kind of an extracellular calmodulin-binding protein (CaMBP). Furthermore, using Northern blot analysis, we examined the expression dynamics of ecbp21 during the incubation of Angelica suspension-cultured cells and the treatments with some growth regulators. The above studies further provide the molecular evidence for the existence of the gene coding for extracellular CaMBPs and imply a possible role for ECBP21.

  Effects of oxypeucedanin on hKv1.5 and action potential duration.:Biol Pharm Bull. 2005 Apr;28(4):657-60.

 A furocoumarin derivative, oxypeucedanin, was purified from Angelica dahurica, and its effects on the human Kv1.5 (hKv1.5) channel and on the cardiac action potential duration (APD), were examined using the patch-clamp technique and the conventional microelectrode technique. Oxypeucedanin inhibited the hKv1.5 current in a concentration-dependent manner, with an IC(50) value of 76 nM, while it had no effect on human eag-related gene (HERG) current. Oxypeucedanin induced an initial fast decline of hKv1.5 current during depolarizations. The inhibition of hKv1.5 channel by oxypeucedanin was voltage-dependent, especially at depolarizing pulses between -40 and 0 mV which corresponds to the voltage range of the channel's opening. Oxypeucedanin also slowed the deactivation time course, resulting in a tail crossover phenomenon. Additionally, oxypeucedanin prolonged the APD of rat atrial and ventricular muscles in a dose-dependent manner. These results suggest that oxypeucedanin is a kind of open-channel blocker of the hKv1.5 channel and it prolongs the APD; therefore, it is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.

  Extraction of coumarins from Angelica dahurica by supercritical extraction and GC-MS analysis.:Zhongguo Zhong Yao Za Zhi. 2004 Mar;29(3):241-4. Chinese.Liu HM, Zhang MX.Biochemical Engineering College of Beijing Union University, Beijing 100023, China. hgthong-mei@buu.com.cn

 OBJECTIVE: To extract coumarins from Angelica Dahurica by supercritical CO2. METHOD: Six-factor and three-level orthogonal experimental design was used to optimize the SFE conditions as guided by the content of total coumarins in the extract. Constituents of the coumarins were analyzed by GC-MS, and their relative contents were determined by normalization method of areas. RESULT: Total 15 coumarins were separated, the relative contents of oxyimperatorin, imperatorin and isoimperatorin being up to 42.40%, 22.14% and 12.12% respectively. Optimum extraction process was established: 21 MPa as extraction pressure, 50 degrees C as extraction temperature, 3 h as time for extraction, 20 mesh as pulverized degree, 6.5 MPa as separation pressure and 30 degrees C as separation temperature. CONCLUSION: Changes in extraction pressure, temperature, time, pulverized degree and separation pressure affect the extracting results remarkably.

  Agents protecting against sepsis from the roots of Angelica dahurica.:Biol Pharm Bull. 2005 Feb;28(2):380-2.

 In the course of isolating agents preventing sepsis from the EtOAc extract of the roots of Angelica dahurica, four known furanocoumarins, isoimperatorin (1), oxypeucedanin (2), (+/-)-byakangelicin (3), and (+)-oxypeucedanin hydrate (4), were isolated as active compounds based on the in vivo assay model of sepsis induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN). Among them, 3 showed the highest survival rate (100% with a dose of 30 mg/kg versus 20% for the control experiment) and decreased the plasma levels of tumor necrosis factor-alpha and alanine aminotransferase in mice adminstered LPS/D-GalN.


  Cytotoxic coumarins from the root of Angelica dahurica.:Arch Pharm Res. 2004 Dec;27(12):1211-5.

 Ten coumarins were isolated from the root of Angelica dahurica by repeated silica gel column chromatography. Their chemical structures were elucidated on the basic of physicochemical and spectroscopic data. Among them, oxypeucedanin hydrate acetonide (7) was isolated for the first time from this plant. Cytotoxicity of coumarins isolated were determined in vitro against L1210, HL-60, K562, and B16F10 tumor cell lines by MTT method. Pangelin (5) and oxypeucedanin hydrate acetonide (7) showed a potent cytotoxic activity with the IC50 values of 8.6 to 14.6 microg/mL against four kinds of tumor cell lines. Other compounds showed the moderate cytotoxic activity or no activity against the tumor cell lines.

  Preparative isolation and purification of coumarins from Angelica dahurica (Fisch. ex Hoffn) Benth, et Hook. f (Chinese traditional medicinal herb) by high-speed counter-current chromatography.:J Chromatogr A. 2004 Oct 15;1052(1-2):223-7. Liu R, Li A, Sun A.Department of Chemistry, College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, Shandong, PR China. renminliu@lctu.edu.cn

 A preparative high-speed counter-current chromatography (HSCCC) method for isolation and purification of coumarins from Angelica dahurica (Fisch. ex Hoffin) Benth, et Hook. f(Baizhi in Chinese) was successfully established by using n-hexane-methanol-water as the two-phase solvent system in gradient elution mode. The upper phase of n-hexane-methanol-water (5:5:5, v/v) was used as the stationary phase of HSCCC. The mobile phase used in HSCCC was the lower phase of n-hexane-methanol-water (5:5:5, v/v) and n-hexane-methanol-water (5:7:3, v/v) that was changed in gradient. Three major components including imperatorin, isoimperatorin and oxypeucedanine were isolated, each at over 98% purity as determined by high-performance liquid chromatography (HPLC). The peak fractions of HSCCC were identified by 1H-NMR and 13C-NMR.

  The herbalogical textual research on "bai zhi".:Zhong Yao Cai. 2004 May;27(5):382-5. Chinese.Wang M, Jia M.Pharmacy school, Shanghai Jiaotong University, Shanghai 200030.

 The folowing grounds of "Bai Zhi" (Angelica dahurica) have been researched on the herbalogy, such as medicinal and cultivated history, change of original plant, collecting time, processing method, quality assessement and medicinal part etc.

  Tyrosinase-inhibitory furanocoumarin from Angelica dahurica.:Biol Pharm Bull. 2004 Jul;27(7):1144-6.

 An extract of the roots of Angelica dahurica BENTH. et HOOK. (Umbelliferae) showed potential tyrosinase inhibition against mushroom tyrosinase. Employing a bioassay-linked HPLC method, followed by semipreparative HPLC, the active principle was isolated and characterized as 9-hydroxy-4-methoxypsoralen.

  Natural medicine: the genus Angelica.:Curr Med Chem. 2004 Jun;11(11):1479-500.Sarker SD, Nahar L.Phytopharmaceutical Research Laboratory, School of Pharmacy, The Robert Gordon University, Schoolhill, Aberdeen AB10 1FR, Scotland, UK. s.sarker@rgu.ac.uk

 More than 60 species of medicinal plants belong to the genus Angelica (Family: Apiaceae). Many of these species have long been used in ancient traditional medicine systems, especially in the far-east. Various herbal preparations containing Angelica species are available over-the-counter, not only in the far-eastern countries, but also in the western countries like USA, UK, Germany, etc. For centuries, many species of this genus, e.g. A. acutiloba, A. archangelica, A. atropupurea, A. dahurica, A. japonica, A. glauca, A. gigas, A. koreana, A. sinensis, A. sylvestris, etc., have been used traditionally as anti-inflammatory, diuretic, expectorant and diaphoretic, and remedy for colds, flu, influenza, hepatitis, arthritis, indigestion, coughs, chronic bronchitis, pleurisy, typhoid, headaches, wind, fever, colic, travel sickness, rheumatism, bacterial and fungal infections and diseases of the urinary organs. Active principles isolated from these plants mainly include various types of coumarins, acetylenic compounds, chalcones, sesquiterpenes and polysaccharides. This review evaluates the importance of the genus Angelica in relation to its traditional medicinal uses, alternative medicinal uses in the modern society and potential for drug development, and summarises results of various scientific studies on Angelica species or Angelica-containing preparations for their bioactivities including, antimicrobial, anticancer, antitumour, analgesic, anti-inflammatory, hepatoprotective, nephroprotective, etc.


  Immunohistochemical analysis and immuno-gold localization of ECBP21 in Angelica dahurica.:Shi Yan Sheng Wu Xue Bao. 2004 Feb;37(1):22-8. Chinese.Ding CB, Mao GH, Sun DY.Institute of Molecular Cell Biology, Hebei Normal University, Shijiazhuang 050016.

 ECBP21 is a calmodulin binding protein (CaMBP) purified from extracellular extracts of suspension-cultured cells of Angelica dahurica, and it is the first reported extracellular CaMBP in plant kingdom. We have recently cloned the full-length cDNA for ECBP21. In this work, using recombinant ECBP21 we prepared rabbit antiserum with high specificity and high titer against ECBP21, and investigated the organ-specific distribution of ECBP21 in Angelica dahurica. ECBP21 was found in all organs examined, particularly abundant in the leaves flowers, and raches, and less in the roots. It was also found in all cells examined, and particularly enriched in the cell wall. These data support the notion that ECBP21 is specifically localized extracellularly, and imply that it may be involved in plant growth and development. In addition, using immunogold transmission electron microscopy method, we studied the subcellular localization of ECBP21 in rachis cells of Angelica dahurica. The results indicated that the ECBP21 was mainly localized in cell wall; this provided a direct evidence of the extracellular existence of ECBP21.

  The anti-staphylococcal activity of Angelica dahurica (Bai Zhi).:Phytochemistry. 2004 Feb;65(3):331-5.Lechner D, Stavri M, Oluwatuyi M, Pereda-Miranda R, Gibbons S.Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.

 Bioassay-guided fractionation of a hexane extract prepared from the roots of the Chinese drug Angelica dahurica (Bai Zhi) led to the isolation of the polyacetylenic natural product falcarindiol (1). The absolute stereochemistry of this compound was confirmed by careful 1H NMR analysis of its (R)- and (S)-Mosher ester derivatives as the 3(R), 8(S) isomer. Activity was tracked using a Mycobacterium fortuitum screening assay and the purified product was evaluated against multidrug-resistant and methicillin-resistant strains of Staphylococcus aureus (MRSA). The minimum inhibitory concentrations (MIC) of this metabolite ranged from 8 to 32 microg/ml highlighting the potential of the acetylene natural product class as antibiotic-lead compounds. These MIC values compare favourably with some of the newest agents in development for the treatment of MRSA infection and indicate that further evaluation of the antibiotic activity of acetylenes is warranted.

  Influence of traditional Chinese anti-inflammatory medicinal plants on leukocyte and platelet functions.:J Pharm Pharmacol. 2003 Sep;55(9):1275-82.Prieto JM, Recio MC, Giner RM, M¨¢?ez S, Giner-Larza EM, R¨ªos JL.Departament de Farmacologia, Facultat de Farm¨¤cia, Universitat de Val¨¨ncia, Burjassot, Spain.

 The enzymes 5-lipoxygenase and elastase are therapeutic targets in dermatological disorders such as psoriasis. Fifteen extracts from traditional Chinese medicinal plants used to treat topical inflammations were screened for their inhibitory effect on lipoxygenase, cyclooxygenase and elastase activity in intact leukocytes and platelets. Astragalus membranaceus, Forsythia suspensa and Poria cocos inhibited 5-lipoxygenase, with IC50 values of 141, 80 and 141 microg mL(-1), respectively. The latter two species, along with Angelica dahurica and Angelica pubescens, also inhibited elastase (IC50 values of 80, 123, 68 and 93 microg mL(-1), respectively), while A. pubescens, Atractylodes macrocephala, Lentinus edodes, Rehmannia glutinosa and Paeonia lactiflora selectively inhibited 12-(S)-HHTrE production, a valid marker of cyclooxygenase activity. The inhibition of phospholipase A(2) activity by P. cocos is discussed. Dehydrotumulosic and pachymic acids, which have been isolated from P. cocos, were shown to inhibit leukotriene B(4) release. The results indicate that both P. cocos and F. suspensa are potentially valuable species in the management of skin pathologies involving chronic inflammation.

  Inhibitory effects of furanocoumarins isolated from the roots of Angelica dahurica on prostaglandin E2 production.:Planta Med. 2003 May;69(5):408-12.

 We have isolated five furanocoumarins, byakangelicin, phellopterin, imperatorin, isoimperatorin, and oxypeucedanin methanolate, from the roots of Angelica dahurica (Umbelliferae) and prepared five semi-synthesized compounds by the partial reduction of each isolated furanocoumarin, and the effects of these compounds on lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2 ) production in rat peritoneal macrophages were examined. Among these compounds, imperatorin showed the most potent inhibitory activity on the LPS-induced PGE2 production. It also inhibited the LPS-induced expressions of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES). These findings suggest that the inhibitory effect of furanocoumarins on the LPS-induced PGE2 production is due to the inhibition of the expression of COX-2 and mPGES.

  Studies on original plant of traditional Chinese drug "bai zhi" (radix Angelicae Dahuricae) and its closely related wild plants. II. Karyological and pollen morphological studies on "bai zhi" and closely related wild plants.:Zhongguo Zhong Yao Za Zhi. 2001 Sep;26(9):584-8. Chinese.Wang NH, Qin HZ, Shu P, Huang LQ, Wang M, Yuan CQ.Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, Jiangsu, China.

 OBJECTIVE: To supplement cytobiological and pollen morphological data for confirming the original plant of traditional Chinese drug "Bai Zhi". METHOD: Karyological study and pollen observation were made on "Bai Zhi" and its closely related wild plants. RESULT: Similarities and differences of "Bai Zhi" and its closely related wild plants were found. CONCLUSION: 1. 4 cultivated breeds of "Bai Zhi", Angelica dahurica, A. dahurica var. formosana, A. porphyrocaulis are really closely related plants. 2. A. dahurica var. formosana is closer to traditional Chinese drug "Bai Zhi" than others.


  Studies on original plant of traditional Chinese drug "bai zhi" (radix Angelicae Dahuricae) and its closely related wild plants. I. Morphological and anatomical studies on "bai zhi" and closely related wild plants.:Zhongguo Zhong Yao Za Zhi. 2001 Aug;26(8):529-33. Chinese.Wang NH, Qin HZ, Huang LQ, Yuan CQ, Wang M, Li BY.Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, Jiangsu, China.

 OBJECTIVE: To supplement morphological and anatomical data for confirming the original plant of traditional Chinese drug "Bai Zhi" (Radix Angelicae Dahuricae). METHOD: Morphologocal observation and anatomical study were made on 4 cultivated breeds and closely related wild plants of "Bai Zhi". RESULT: According to morphological and anatomical characteristics discovered in this paper, 7 samples noted above could be divided into 3 groups: 1. 4 breeds ("Chuan Bai Zhi", "Hang Bai Zhi", "Qi Bai Zhi" and "Yu Bai Zhi") and Angelica dahurica var. formosana; 2. A. dahurica; 3. A. porphyrocaulis. CONCLUSION: In the morphological and anatomical point of view, A. dahurica var. formosana is closer to traditional Chinese drug "Bai Zhi" than others.

  Studies on original plant of traditional Chinese drug "bai zhi" (radix Angelicae Dahuricae) and its closely related wild plants. IV. Discussion on original plant and cultivation history of traditional Chinese drug "bai zhi" and evolution of its closely related wild plants.:Zhongguo Zhong Yao Za Zhi. 2001 Nov;26(11):733-6. Chinese.Wang NH, Huang LQ, Yang B, Baba K, Taniguchi M, Yuan CQ, Qin HZ, Shu P.Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, Jiangsu, China.

 OBJECTIVE: To confirm the original plant of traditional Chinese drug "Bai Zhi" and to inquire into the cultivation history of "Bai Zhi" and evolution of closely related wild plants of "Bai Zhi". METHOD: Various research results obtained were synthesized and discussed according to historical and current data. RESULT: Obtained research results, historical and current data showed almost no difference. CONCLUSION: 1. Angelica dahurica var. formosana must be the original plant of traditional Chinese drug "Bai Zhi". 2. A. porphyrocaulis should be treated as a variety of A. dahurica, named as A. dahurica var. porphyrocaulis. 3. 4 sorts of Chinese traditional drug "Bai Zhi" (Chuang Bai Zhi, Hang Bai Zhi, Qi Bai Zhi and Yu Bai Zhi) should not be taxonomically distinguished. The history of utilization and cultivation of "Bai Zhi", and the evolutional relation of the closely related wild plants of "Bai Zhi" (A. dahurica, A. dahurica var. formosana, and A. dahurica var. porphyrocaulis) were also discussed.

  Studies on original plant of traditional Chinese drug "bai zhi" (radix Angelicae Dahuricae) and its closely related wild plants. III. Comparison of coumarins of "bai zhi" with those of closely related wild plants.:Zhongguo Zhong Yao Za Zhi. 2001 Oct;26(10):669-71. Chinese.Wang NH, Taniguchi M, Yang B, Huang LQ, Yuan CQ, Baba K.Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, 210014, Jiangsu, China.

 OBJECTIVE: To provide chemical data for confirming the original plant of traditional Chinese drug "Bai Zhi". METHOD: Coumarins of 4 cultivated breeds of "Bai Zhi" and 3 closely related wild plants, together with other 2 Angelica plants were compared by HPLC. RESULT: According to coumarin patterns, 4 cultivated breeds of "Bai Zhi" and 3 closely related wild plants could be divided into 3 groups: 1. 4 cultivated breeds of "Bai Zhi" ("Chuan Bai Zhi", "Hang Bai Zhi", "Qi Bai Zhi" and "Yu Bai Zhi") and Angelica dahurica var. formosana; 2. A. dahurica; 3. A. porphyrocaulis. CONCLUSION: In point of the coumarin components, A. dahurica var. formosana is closer to traditional Chinese drug "Bai Zhi" than the others.

  Studies on chemical constituents from the water-soluble part of root of Angelica dahurica.:Zhongguo Zhong Yao Za Zhi. 2002 Apr;27(4):279-80. Chinese.You XL, Li L, Xiao YQ.Institute of Chinese Materia Medica, China Academy of Traditional Chinese Medicine, Beijing 100700, China.

 OBJECTIVE: To study the chemical constituents in the root of Angelica dahurica. METHOD: The compounds were isolated and identified by column chromatography and 1H, 13C NMR data. RESULT: Eleven compounds were isolated and identified. CONCLUSION: Six compounds were isolated from this plant for the first time.

  Anti-acne effects of Oriental herb extracts: a novel screening method to select anti-acne agents.:Skin Pharmacol Appl Skin Physiol. 2003 Mar-Apr;16(2):84-90.

 The acne-therapeutic effects of Oriental herb extracts were investigated in terms of antichemotactic effect on polymorphonuclear leucocytes, antilipogenic actions, antibacterial activity against Propionibacterium acnes and resistance induction potency in the bacteria. The ethanol extract (0.01%) of Angelica dahurica markedly suppressed neutrophil chemotaxis, comparable to the effect of erythromycin (0.01%), whereas a strong antilipogenic effect was obtained with rhizoma coptidis (Coptis chinensis) extract (0.01%), leading to a higher efficacy than that of retinoic acid (0.01%). Interestingly, only Glycyrrhiza glabra showed a remarkable antibacterial activity against P. acnes, resulting in negligible induction of resistance, in comparison with a marked development of resistance in the bacteria treated with erythromycin. We suggest that an appropriate formulation containing A. dahurica, rhizoma coptidis and G. glabra could be helpful for the prevention and treatment of acne lesions.


  Experiment on polyploid induction of Angelica dahurica var. formosana.:Zhong Yao Cai. 1999 Dec;22(12):611-2. Chinese.Peng F, Zhou R, Liu J.Hunan College of Traditional Chinese Medicine, Changsha 410004.

 Colchicine solution was applied to the primary adventitious buds of Angelica dahurica var. formosana in vitro to induce the polyploid. Compared with non-treated plantlet, the morphology, microhisology, and chromosome number of treated plantlets are varied. It proved that the polyploid induction was effective.

  Acetylcholinesterase inhibitors from the roots of Angelica dahurica.:Arch Pharm Res. 2002 Dec;25(6):856-9.

 In the course of finding Korean natural products for acetylcholinesterase (AChE) inhibitory activity, we found that a methanolic extract of the roots of Angelica dahurica showed significant inhibitory effects on AChE. Bioassay-guided fractionation of the methanolic extract resulted in the isolation of three furanocoumarins, isoimperatorin (1), imperatorin (2) and oxypeucedanin (3), as active principles. These compounds inhibited AChE activity in a dose-dependent manner, and the IC50 values of compounds 1-3 were 74.6, 63.7 and 89.1 microM, respectively.

  Inhibition of Trypanosoma cruzi growth by medical plant extracts.:Fitoterapia. 2002 Dec;73(7-8):569-75.Schinella GR, Tournier HA, Prieto JM, R¨ªos JL, Buschiazzo H, Zaidenberg A.C¨¢tedra de Farmacolog¨ªa, Facultad de Ciencias M¨¦dicas, Universidad Nacional de La Plata, Calles 60 y 120, La Plata 1900, Argentina. schinell@lacasilla.com.ar

 This study describes the screening of extracts obtained from 18 plants and two fungi used in the Chinese and Mediterranean traditional medicines on epimastigote forms of Trypanosoma cruzi. The extracts were tested against epimastigote of T. cruzi Bra C15C2 clone in vitro at 27 degrees C and at a concentration of 250 microg/ml in axenic culture. Angelica dahurica, A. pubescens, A. sinensis, Astragalus membranaceus, Coptis chinensis, Haplophyllum hispanicum, Phellodendron amurense, Poria cocos, Ranunculus sceleratus and Scutellaria baicalensis showed significant effects against the parasite with a percentage of growth inhibition between 20 and 100%. C. chinensis and R. sceleratus showed the greatest activity with IC(50) values of 1.7 microg/ml for C. chinensis and 10.7 microg/ml for R. sceleratus. These activities are greater than that of allopurinol. C. chinesis and R. sceleratus extracts did not show cytotoxic effects on rat polimorphonuclear cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactic dehydrogenase assays. These results allowed us to suggest that R. sceleratus and C. chinensis could be a source of new compounds clinically active against T. cruzi. Copyright 2002 Elsevier Science B.V.

  Byakangelicol, isolated from Angelica dahurica, inhibits both the activity and induction of cyclooxygenase-2 in human pulmonary epithelial cells.:J Pharm Pharmacol. 2002 Sep;54(9):1271-8.Lin CH, Chang CW, Wang CC, Chang MS, Yang LL.Graduate Institute of Biomedical Technology, Taipei Medical University, Taiwan.

 We examined the inhibitory mechanism of byakangelicol, isolated from Angelica dahurica, on interleukin-1beta (IL-1beta)-induced cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) release in human pulmonary epithelial cell line (A549). Byakangelicol (10-50 microM) concentration-dependently attenuated IL-1beta-induced COX-2 expression and PGE2 release. The selective COX-2 inhibitor, NS-398 (0.01-1 microM), and byakangelicol (10-50 microM) both concentration-dependently inhibited the activity of the COX-2 enzyme. Byakangelicol, at a concentration up to 200 microM, did not affect the activity and expression of COX-1 enzyme. IL-1beta-induced p44/42 mitogen-activated protein kinase (MAPK) activation was inhibited by the MAPK/extracellular signal-regulated protein kinase (MEK) inhibitor, PD 98059 (30 microM), while byakangelicol (50 microM) had no effect. Treatment of cells with byakangelicol (50 microM) or pyrrolidine dithiocarbamate (PDTC; 50 microM) partially inhibited IL-1beta-induced degradation of IkappaB-alpha in the cytosol, translocation of p65 NF-kappaB from the cytosol to the nucleus and the NF-kappaB-specific DNA-protein complex formation. Taken together, we have demonstrated that byakangelicol inhibits IL-1beta-induced PGE2 release in A549 cells; this inhibition may be mediated by suppression of COX-2 expression and the activity of COX-2 enzyme. The inhibitory mechanism of byakangelicol on IL-1beta-induced COX-2 expression may be, at least in part, through suppression of NF-kappaB activity. Therefore, byakangelicol may have therapeutic potential as an anti-inflammatory drug on airway inflammation.

  Observation on morphology and histology of Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook. f. var. formosana (Boiss.) Shan et Yuan in the process of in vitro cultivation and polyploid induction.:Zhongguo Zhong Yao Za Zhi. 2000 Jan;25(1):17-20. Chinese. Peng F, Guo Y.Hunan College of Traditional Chinese Medicine, Hunan Changsha 410004, China.

 OBJECTIVE: To explore the relationship between morphogenesis and histogenesis in the process of in vitro cultivation of Angelica dahurica f. var. formosana, and determine the best period for its polyploid induction. METHOD: In the different periods of in vitro cultivation, the explants were obtained and their sections observed. When the adventitiousbuds began to differentiate, aqueous solution was applied for polyploid induction. RESULT: The adventitious buds were mainly externally originated and thus fit for polyploid induction. The most appropriate period for induction was around the 38th day of cultivation. CONCLUSION: Induction treatment can be used as an effective biotechnological approach to adventitious buds in the process of tissue cultivation.


  RAPD analysis of germplasm in "baizhi".:Zhongguo Zhong Yao Za Zhi. 1999 Aug;24(8):457-9, 509-10. Chinese.Huang L, Wang M, Fu G, Yang B, Wang N, Yuan C.Instituute of Chinese Material Medica, China Academy of Traditional Chinese Medicine, Beijing 100700.

 OBJECTIVE: To analyse the germplasm in Baizhi. METHOD: Using 12 random primers, over seventeen individuals' RAPD were detected in four populations from wild Baizhi (Angelica dahurica), Qi Baizhi and Hang Baizhi. RESULTS: A total of 40 loci were amplified, 26 of which were polymorphism(65%). The PPS values of Hang Baizhi and Qi Baizhi indicate their low levels of genetic diversity. According to the RAPDinstance analysis, the genetic distance(0.16) between Qi Baizhi and Hang Baizhi is shorter than that of the individuals of the populations of Qi Baizhi and Hang Baizhi, and all of these genetic distances are shorter than those between wild Baizhi and Hang Baizhi(Qi Baizhi). CONCLUSION: Hang Baizhi- and Qi Baizhi belong to the same taxon, which is different from the wild Baizhi.

  Imperatorin, a furanocoumarin from Angelica dahurica (Umbelliferae), induces cytochrome c-dependent apoptosis in human promyelocytic leukaemia, HL-60 Cells.:Pharmacol Toxicol. 2002 Jul;91(1):40-8.

 Imperatorin, a biologically active furanocoumarin from the roots of Angelica dahurica (Umbelliferae), was found to induce apoptosis in human promyelocytic leukaemia, HL-60 cells. DNA fragmentation assay, morphology-based evaluation, and flow cytometric analysis demonstrated that imperatorin at micromolar concentrations was able to trigger apoptosis of HL-60 cells. Neither necrosis nor differentiation was observed at cytotoxic micromolar concentrations of imperatorin. Further studies showed that the cytochrome c/caspase-9 pathway was responsible for imperatorin-induced apoptosis; i.e., mitochondrial membrane was depolarized, Bcl-2 was down-regulated, cytochrome c was released from mitochondria, caspase-9 and caspase-3 were activated, and poly(ADP-ribose) polymerase was cleaved. Furthermore, imperatorin-induced apoptosis was significantly blocked by Z-VAD-FMK (a broad spectrum caspase inhibitor), Z-LEHD-FMK (a caspase-9 inhibitor) and Ac-DMQD-CHO (a caspase-3 inhibitor), but not by Z-IEDT-FMK (a caspase-8 inhibitor).

  Pharmacokinetic interactions between herbal remedies and medicinal drugs.:Xenobiotica. 2002 Jun;32(6):451-78. Review.Ioannides C.Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford GU2 7XH, UK. c.ioannides@surrey.ac.uk

 1. The use of herbal products to treat a wide range of conditions is rising rapidly, leading to increased intake of phytochemicals. Recent studies revealed potentially fatal interactions between herbal remedies and traditional drugs. 2. In transplant patients, self-medication with St John's wort (Hypericum perforatum) has led to a drop in plasma levels of the immunosuppressant drug cyclosporine, causing tissue rejection. 3. Intake of St John's wort increases the expression of intestinal P-glycoprotein and the expression of CYP3A4 in the liver and intestine. The combined up-regulation in intestinal P-glycoprotein and hepatic and intestinal CYP3A4 impairs the absorption and stimulates the metabolism of cyclosporine, leading to subtherapeutic plasma levels. The St John's wort component, hyperforin, contributes to the induction of CYP3A4. 4. St John's wort also enhances the metabolism of other CYP3A4 substrates including the protease inhibitors indinavir and nevirapine, oral contraceptives, and tricyclic antidepressants such as amitriptyline. 5. Other herbal remedies with the potential to modulate cytochrome P450 activity and thus participate in interactions with conventional drugs include Milk thistle, Angelica dahurica, ginseng, garlic preparations, Danshen and liquorice. 6. Herbal products are currently not subject to the rigorous testing indispensable for conventional drugs. However, if potential drug interactions are to be predicted, it is essential that the ability of herbal products to interfere with drug-metabolizing enzyme systems is fully established.

  Furocoumarins from Angelica dahurica with hepatoprotective activity on tacrine-induced cytotoxicity in Hep G2 cells.:Planta Med. 2002 May;68(5):463-4.

 Fractionation of the MeOH extract of Angelica dahurica Benth et Hook resulted in the isolation of six furocoumarins, imperatorin (1), isoimperatorin (2), (+/-)-byakangelicol (3), (+)-oxypeucedanin (4), (+)-byakangelicin (5), and (+)-aviprin (6). Among these, compounds 1 and 5 exhibited strong hepatoprotective activities, displaying EC(50) values of 36.6 +/- 0.98 and 47.9 +/- 4.6 microM, respectively. Compounds 3 and 4 showed moderate activities with EC(50) values of 112.7 +/- 5.35 and 286.7 +/- 6.36 microM, respectively. Silybin as a positive control showed the EC(50) value with 69.0 +/- 3.4 microM. Comparison of hepatoprotective activities for six furocoumarins 1 - 6 suggested that oxy-substitution at the C-9 position increased the hepatoprotective activity.

  A new coumarin from the stem of Angelica dahurica.:Arch Pharm Res. 2002 Feb;25(1):53-6.

 One new and three known coumarins were isolated from the CHCl3 soluble fraction of Angelica dahurica stem. On the basis of spectral data, the structures of the isolated compounds were determined to be scopoletin, angelol I, angelol H and 6-[(1S), 2(R)-2, 3-dihydroxy-1-methoxy-3-methylbutyl]-7-methoxycoumarin; the latter being isolated for the first time from a plant source.


  Inhibitory potential of herbal medicines on human cytochrome P450-mediated oxidation: properties of umbelliferous or citrus crude drugs and their relative prescriptions.:Jpn J Pharmacol. 2001 Apr;85(4):399-408.

 To investigate the possible drug interaction with herbal medicine, hot water decoctions or 40% ethanol infusions of several Umbelliferous or Citrus crude drugs and their prescriptions were examined in vitro for their abilities to inhibit human cytochrome P450 3A (CYP3A). Addition of each decoction or infusion from Baizhi (Angelica dahurica and varieties), Qianghuo (Notopterygium incisum or N. forbesii), Duhuo (Angelica biserrata), Fangfeng (Saposhnikovia divaricata), Danggui (Angelicasinensis), Zhishi or Zhiqiao (Citrus aurantium) resulted in various degrees of human CYP3A inhibition as determined by microsomal testosterone 6beta-hydroxylation. The inhibitory potency was consistent with the abundance of the hydrophobic components for each sample. Experiments on the infusion of a Japanese Baizhi (BZ1) showed the major role of furanocoumarins on human CYP3A inhibition. Some of the crude drugs and a related prescription showed increased inhibition after the preincubation, suggesting the involvement of a mechanism-based inhibition. Some formulated prescriptions, however, showed intense inhibition with their hydrophobic fractions rather than with their hydrophobic fractions, suggesting that components other than furanocoumarins in herbal prescriptions may also cause CYP3A inhibition. These results indicate the necessity of intensive investigations on the possible drug interaction with traditional medicines.

  Simultaneous determination of byak-angelicin and oxypeucedanin hydrate in rat plasma by column-switching high-performance liquid chromatography with ultraviolet detection.:J Chromatogr B Biomed Sci Appl. 2001 Apr 5;753(2):309-14.

 A simple and sensitive column-switching HPLC method was developed for the simultaneous determination of two furocoumarin compounds, byak-angelicin and oxypeucedanin hydrate, which are the main components of hot water extract of Angelica dahurica root (AE), in rat plasma. Plasma sample was simply deproteinated with perchloric acid. After centrifugation, the supernatant was injected into a column-switching HPLC system consisting of a clean-up column (Symmetry Shield RP 8, 20x3.9 mm I.D.) and analytical column (Symmetry C18, 75x4.6 mm I.D.) which were connected with a six-port switching valve. The flow-rate of the mobile phase (acetonitrile-water, 20:80) was maintained at 1 ml/min. Detection was carried out at wavelength 260 nm with a UV detector. The column temperature was maintained at 40 degrees C. The calibration curves of byak-angelicin and oxypeucedanin hydrate were linear over the ranges 19.6 to 980 ng/ml (r2>0.997). The accuracy of these analytes was less than 4.4%. The intra- and inter-day relative standard deviations of byak-angelicin and oxypeucedanin hydrate were within 12.0% and 12.7%, respectively. The present method was applied for the analysis of plasma concentration from rats after administration of AE.

  Furanocoumarins from the root of Angelica dahurica.:Arch Pharm Res. 2000 Oct;23(5):467-70.

 Five furanocoumarins including a new one were isolated from the root of Angelica dahurica by repeated silica gel column chromatography. Their chemical structures were determined to be isoimperatorin (1), oxypeucedanin hydrate-3"-butyl ether (2), imperatorin (3), knidilin (4), and oxypeucedanin hydrate (5). This represents the first study in which the compound 2 has been isolated and identified. The long-range coupling (5J) in the 1H-NMR spectrum observed in the linear furanocoumarin skeleton was also investigated in detail.

  Influence of sulphur smoking on the content of coumarins in the root of Angelica dahurica (Fisch. ex Hoffm.) Benth. et Hook.f.var. formosana (Boiss) Shan et Yuan.:Zhongguo Zhong Yao Za Zhi. 1997 Sep;22(9):536-8, 575. Chinese.Zhang Y, Yu H.Institute of Medicinal Plant Cultivation, Sichuan Academy of Traditional Chinese Medicine, Nanchuan.

 The content of coumarins in the root of Angelica dahurica (Ad) treated in different time spans with smoke of sulphur was determined by HPLC. The result showed that in nine hours before Ad was smoked thoroughly the content of coumarins reduced rapidly with the increase of time, and there after, the reduction was not obvious. After being treated for nine hours, the total coumarins were reduced by 75.3% and after forty hours the ratio reached 77.9%.

  Interaction of drugs and Chinese herbs: pharmacokinetic changes of tolbutamide and diazepam caused by extract of Angelica dahurica.:J Pharm Pharmacol. 2000 Aug;52(8):1023-9.

 The inhibitory effects of Angelica dahurica root extract on rat liver microsomal cytochrome P450 and drug-drug interactions were studied. The 2alpha- and 16alpha-hydroxylase activity of testosterone were most strongly inhibited, with 17.2% and 28-5% of their activity remaining, respectively, after oral administration of A. dahurica extract at a 1 g kg(-1) dose. 6beta-Hydroxylase activity was also inhibited, with 70% of its activity remaining, under the same conditions. In addition, treatment with the extract inhibited the metabolism of tolbutamide, nifedipine and bufuralol. These results showed that the extract inhibited the various isoforms of cytochrome P450 such as CYP2C, CYP3A and CYP2D1. The A. dahurica extract delayed elimination of tolbutamide after intravenous administration at a 10 mg kg(-1) dose to rats. Thus, the extract altered the liver intrinsic clearance. It had little effect, however, on the pharmacokinetic parameters of diazepam after intravenous administration at 10 mg kg(-1). Since diazepam showed high clearance, it underwent hepatic blood flow rate-limited metabolism. Therefore, the change of intrinsic clearance had little effect on hepatic clearance. However, the Cmax value after oral administration of diazepam with extract treatment was four times that with non-treatment. It was suggested that the first-pass effect was changed markedly by the extract. High-dose (1 g kg(-1)), but not low dose (0.3 g kg(-1)), administration of A. dahurica extract increased significantly the duration of rotarod disruption following intravenous administration of diazepam at 5 mg kg(-1). It was concluded that administration of A. dahurica extract has the potential to interfere with the metabolism, by liver cytochrome P450, of other drugs.


  Histamine-release effectors from Angelica dahurica var. dahurica root.:J Nat Prod. 1997 Mar;60(3):249-51.

 Six compounds isolated from the EtOAc fraction of the dried roots of Angelica dahurica var. dahurica inhibited compound 48/80-induced histamine levels in mouse peritoneal cavity (in vivo). Bergapten, oxypeucedanin hydrate, and byakangelicin inhibited compound 48/80-induced histamine elevation at a dose of 25 mg/kg. Conversely, sec-O-acetylbyakangelicin [8-(2-acetoxy-3-hydroxy-3-methylbutoxy)-5-methoxypsoralenI enhanced compound 48/80-induced histamine elevation at a dose of 25 mg/kg, while phellopterin and oxypeucedanin had no effect.

  Antimicrobial constituents of Angelica dahurica roots.:Phytochemistry. 1997 Mar;44(5):887-9.

 One novel coumarin from Angelica dahurica roots was elucidated to be 5,8-di(2,3-dihydroxy-3-methylbutoxy)-psoralen. It occurs together with six other known coumarins and ferulic acid. The antimicrobial activity of the coumarins and ferulic acid were compared.

  Furanocoumarins with affinity to brain benzodiazepine receptors in vitro.:Phytochemistry. 1997 Mar;44(6):1121-4.Bergendorff O, Dekermendjian K, Nielsen M, Shan R, Witt R, Ai J, Sterner O.Division of Organic Chemistry 2, University of Lund, Sweden

 Eight furanocoumarins were isolated from a methanol extract of dried roots of Angelica dahurica. One of these, phellopterin, strongly (IC50 = 0.36 microM) inhibits the binding of [3H]diazepam to central nervous system benzodiazepine receptors in vitro, while the others, despite their structural similarities with phellopterin, are considerably less active.

  Characterisation of the furanocoumarin phellopterin as a rat brain benzodiazepine receptor partial agonist in vitro.:Neurosci Lett. 1996 Nov 29;219(3):151-4. Dekermendjian K, Ai J, Nielsen M, Sterner O, Shan R, Witt MR.Department of Biochemistry, St. Hans Hospital, Roskilde, Denmark.

 Phellopterin, a naturally occurring furanocoumarin found in the roots of Angelica dahurica, inhibits [3H]diazepam and ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate ([3H]Ro 15-1788) binding to the benzodiazepine site of the rat brain gamma-aminobutyric acidA (GABAA) receptor in vitro with IC50 values of 400 and 680 nM, respectively. Two other naturally occurring furanocoumarins, byakangelicol and imperatorin were significantly less potent, with IC50 values for inhibition of [3H]diazepam binding of 8.0 and 12.3 microM, respectively. Scatchard plot analysis showed that the inhibitory activity of phellopterin was due to competitive inhibition of the benzodiazepine ligand binding. The results of GABA- and t-butylbicyclophosphorothionate (TBPS)-shift assays suggest that phellopterin is a partial agonist of the central benzodiazepine receptors in vitro.

  56.Effect of some drugs on electroacupuncture analgesia and cytosolic free Ca2+ concentration of mice brain.:Hu J, Xie J, Hu J, Zhang Y, Wang J, Chen R.Hospital affiliated to Zhenjiang Medical College.

 In this paper, the effects of some analgesic drugs such as corydalis yanhusuo, Angelica dahurica and Analginum on electroacupuncture analgesic function were studied. In the meantime, the concentrations of cytosolic free Ca2+ ([Ca2+]i) in mice hypothalamus (HT) and periaqueductual grey (PAG) were determined by use of the fluorescence dye Fura-2/AM and AR-CM cation measurement system. The results showed that Corydalis yanhusuo obviously strengthened the analgesic function produced by electroacupuncture. Besides, the [Ca2+]i in the two brain regions of mice in these analgesic experiments with electroacupuncture and Corydalis yanhusuo were all decreased (compared with saline control group, P < 0.01), In the same experimental condition, the [Ca2+]i in Angelica dahurica group and Analginum group has no significant difference compared with the control group, the analgesic mechanisms may be different from that of electroacupuncture and Corydalis yanhusuo.


  Pharmacological studies on the Chinese drug radix Angelicae dahuricae:Zhongguo Zhong Yao Za Zhi. 1991 Sep;16(9):560-2, 576. Chinese.Li H, Dai Y, Zhang H, Xie C.School of Pharmacy, West China University of Medical Sciences, Chengdu.

 Several species of the Chinese drug Angelica dahurica from different habitats have been studied in terms of anti-inflammatory, analgesic and antipyretic actions and acute toxicity. The medical value of these species is reported in this paper as a guideline for their clinic application.

  Pharmacological activities of water extracts of Umbelliferae plants.:Arch Pharm Res. 1991 Mar;14(1):87-92.

 In order to evaluate the pharmacological activities of Chinese medicine, nine Umbelliferae plants were selected and their restoring activity against dexamethasone-induced disorders, liver protective activity, antimicrobial activity, anti-inflammatory activity and antimutagenic activity were tested and compared. Angelica dahurica. Angelica acutiloba and Ostericum koreanum showed various activities in these tests at the dose used in this study.

  Studies on the antitumor-promoting activity of naturally occurring substances. II. Inhibition of tumor-promoter-enhanced phospholipid metabolism by umbelliferous materials.:Chem Pharm Bull. 1990 Apr;38(4):1084-6.

 Ninety-five extracts prepared from 14 kinds of Umbelliferous materials were studied to determine their effects on tumor-promoter-induced phenomena in vitro. Of the materials, 5 Chinese crude drugs, two Bai-Hua Qian-Hu classified as Q-I and Q-II types, the root of Peucedanum praeruptorum Dunn., Zi-Hua Qian-Hu, the root of P. decursivum Maxim., Tang-Bai-Zhi, the root of Angelica dahurica Benth, et Hook. var. pai-chi Kimura, Hata et Yen., Dang-Gui, the root of A. acutiloba Kitagawa and 2 Umbelliferous plants, ashita-ba. A. keiskei Koidz., and ama-nyuu, A. edulis Miyabe, showed potent inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32Pi incorporation into phospholipids of cultured cells. From the active fraction of the crude drug "Tang-Bai-Zhi," imperation (1), isoimperatoin (2), oxypeucedanin (3), pabulenol (4), neobyakangelicol (5) and byakangelicin (6) were identified as active or inactive principles. Compound 4 had not previously been isolated from Tang-Bai-Zhi, A. dahurica var. pai-chi. We also discuss the structure-activity relationship among the above 6 kinds of linear-type furanocoumarins, together with 3 kinds of antitumor-promoter coumarins having the same skeleton, psoralen (7), bergapten (8) and xanthotoxin (9), obtained from "ashita-ba" (eaten as a vegetable in Japan). Among the compounds in the present experiment, compounds 1 and 2 showed potent inhibitory activity at the concentration of 50 micrograms/ml and 3-9 were found to have less or no activity.

  Reverse-phase HPLC determination of coumarins in the traditional Chinese drug bai-zhi (Angelica dahurica forma bai-zhi).:Yao Xue Xue Bao. 1990;25(2):131-6. Chinese.

 A reversed phase HPLC procedure has been developed for the separation and determination of oxypeucedanin (I), imperatorin (II) and isoimperatorin (III) in Bai-zhi simultaneously. I, II and III were extracted from Bai-zhi by using ether. The solution was evaporated to dryness and the residue was redissolved in 25 ml of ethyl acetate and 10 microliters of the solution were analysed on Waters mu Bondapak C13 column (300 x 3.9 mm ID) using methanol-water (70:30) as the mobile phase and detecting at 254 nm. The results were calculated by external standard method on the basis of peak area. The average recoveries of the standards added to the sample were 101.36, 100.54 and 97.91% for I, II and III respectively, and coefficients of variation were less than or equal to 3.33%. Analytical results by HPLC method are in agreement with those by TLC method. This method is rapid, reproducible and accurate and has been applied to analyse the contents of three components in 42 samples of angelica. The results of fourteen samples were given.

  Effects of Various Coumarins from Roots of Angelica dahurica on Actions of Adrenaline, ACTH and Insulin in Fat Cells.:Planta Med. 1982 Jul;45(7):183-7.

 Experiments were carried out on the effects of various coumarins on the actions of adrenaline, adrenocorticotropic hormone (ACTH) and insulin in fat cells isolated from rats. Furocoumarins such as oxypeucedanin hydrate, bergapten, xanthotoxin, imperatorin, phellopterin activated adrenaline-induced lipolysis. Furocoumarins such as oxypeucedanin hydrate, imperatorin and phellopterin also activated ACTH-induced lipolysis. On the other hand, furocoumarins such as byak-angelicin, neobyakangelicol and isopimpinellin strongly inhibited insulin-stimulated lipogenesis. Therefore, the crude drug "Byakushi" may activate the actions of lipolytic hormones and selectively inhibit the effects of anti-lipolytic hormones.


  Scientific References:

  1.Research Update:Angelica dahurica.